Both clinical and experimental studies have shown that myocardial ischemia induces many metabolic changes including a grater reliance on glucose for energy production. The mechanisms regulating glucose uptake in the ischemic heart are not well defined. Existing data suggest that increases in glucose uptake in response to acute ischemia are probably mediated by the insulin regulatable glucose transporter (GLUT4). However, other studies suggest that chronic hypoxia results in upregulation of the glucose transporter responsible for basal glucose uptake (GLUT1) while GLUT4 is unaffected. The studies outlined in this proposal will examine both acute and chronic ischemic regulation of GLUT1 and GLUT4 transcription, translation and translocation from intracellular pools to the cell surface in clinically relevant models of low flow ischemia. In addition, given the metabolic changes caused by diabetes (decreased myocardial glucose uptake and decreased GLUT1 and GLUT4 content), the effects of diabetes on regulation of GLUT1 and GLUT4 during ischemia will be studied. Specific aims of the proposed research include; 1) development of a new method for more accurate quantification of sarcolemmal glucose transporters based on modification of cell surface proteins.. 2) characterization of the effects of ac ute ischemia on GLUT1 and GLUT4 translocation, 3) determination of diabetes blunts translocation of glucose transporters during ischemia and, 4) determination of the regulation of GLUT1 and GLUT4 expression and location in response to chronic ischemia.